Pathologic hyperprolactinemia in men can be associated with serious reproductive disorders including impotence and hypogonadism. We have developed an animal model for studying the effects of hyperprolactinemia on male reproductive functions. Transplantation of four pituitaries under the kidney capsules of adult male rats or mice produces chronic elevation of peripheral PRL to supraphysiological levels, drastic deficits of copulatory behavior and a reduced ability to release gonadotropins. We will utilize this experimental model to define the mechanisms by which hyperprolactinemia affects reproductive functions in the male. By studying mating behavior in males given pituitary grafts and a drug which inhibits prolactin (PRL) release, we will determine whether deficits in copulatory behavior can indeed be explained by elevated PRL levels. We will also determine whether the stimulation of adrenal growth and function in pituitary grafted males accounts for or contributes to the suppression of mating behavior. Furthermore, we will determine whether replacement therapy with LHRH, hCG or testosterone can stimulate copulatory behavior in hyperprolactinemic males. In a separate series of experiments, we will define the effects of hyperprolactinemia on endogenous LHRH levels, on hypothalamic sensitivity to electrical stimulation and on pituitary responsiveness to LHRH. We will also measure the levels of gonadotropins and gonadotropin receptors, as well as the responsiveness of the testis to gonadotropins in pituitary grafted males. During the proposed period of support, we will initiate pilot studies of hypothalamic, pituitary and testicular function in men with hyperprolactinemia.